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PubMed1986

Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy.

Inland areas of northern California have an intense grass pollination in the spring of each year. This is accompanied by a stirking rise in the incidence of asthma. We documented this relationship and designed a trial to test the efficacy of immunotherapy for grass-pollen asthma. Aeroallergen counts were performed on the roof of the allergy clinic of David Grant Medical Center from January 1981 to December 1984 by a gravity collector. These counts were compared to counts done on a Rotorod at a nearby hospital from July 1982 to September 1984. Climatologic factors were also tabulated. Visits for asthma and rhinitis to our emergency room and asthma admissions to our hospital were counted for the 4-year period. A randomized, double-blinded, placebo-controlled trial of immunotherapy with grass-pollen extract was performed from November 1984 to June 1985. Two groups of clinically and immunologically well-matched subjects were started on an accelerated preseasonal trial of immunotherapy. One group received a standardized grass extract, and the other group did not. Both groups received other extracts of aeroallergens to which they were skin test positive that occur locally in the spring and summer. This was done because of our dissatisfaction with a histamine placebo used in a previous pilot study. Symptom medication scores (SMS) and immunologic parameters were followed. For the 4-year period, grass-pollen count (GPC) correlated strongly with asthma emergency room visits (r = 0.90; p less than 0.001) and for rhinitis (r = 0.92; p less than 0.001). Asthma admissions also correlated strongly with GPC (r = 0.72; p less than 0.001). Other aeroallergens either did not correlate significantly or occurred in such small numbers that they could not be seriously considered. Rotorod counts supported these conclusions with the exceptions of some Basidiomycetes. Climatologic factors demonstrated no relationship to the incidence of asthma. Asthma SMS were lower in the grass-treated group, p less than 0.05. Rhinitis SMS were also lower but did not reach significance, p = 0.11. RGGI sIgE did not rise significantly in the grass-treated group but did in the placebo-treated group. RGGI sIgE rose in both groups, although to significantly higher levels in the grass-treated group, p less than 0.001. The asthma SMS were inversely related to increasing RGGI cumulative dose, p less than 0.10. Linear regression analysis of the dose-response scattergram suggests that a cumulative dose of approximately 90 micrograms of RGGI may be desirable.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1996

Immunologic effects of encapsulated short ragweed extract: a potent new agent for oral immunotherapy.

BACKGROUND: Oral allergen immunotherapy with conventional allergens has not been a useful mode of treatment because of the lack of potency of allergens when administered by this route. OBJECTIVE: To study the immunologic potency of short ragweed pollen extracts microencapsulated by a new technique administered orally to short ragweed pollen-sensitive humans and to establish the dose of oral microencapsulated short ragweed pollen extract required for these effects. METHODS: Nine short ragweed pollen-sensitive patients were treated with a new oral agent for immunotherapy, microencapsulated short ragweed pollen extract, in an open study. The effectiveness of this treatment was determined by comparison to a group of nine matched short ragweed pollen-sensitive patients who received no treatment. Treated patients developed high titers of short ragweed-specific IgG and IgE antibodies and their expected seasonal increase in IgE antibodies was regulated. The dose of microencapsulated short ragweed pollen extract required to achieve these effects was only slightly higher than the dose of short ragweed pollen extract used in high dose subcutaneous immunotherapy. Furthermore, this dose was achieved in 7 weeks. There were no side effects other than mild gastrointestinal ones. The nine treated patients fared clinically better during the ragweed season than the untreated patients in this open study. CONCLUSION: This study suggests that allergens microencapsulated by this new technique may make oral immunotherapy a practical mode of treatment.

Adult↗

PubMed1993

Oral induction of tolerance to nickel sensitization in mice.

Antigen contact via the alimentary tract prior to sensitization may result in systemic immunologic unresponsiveness ("oral tolerance"). The induction of oral tolerance seems an attractive strategy to combat undesired immune responses, such as allograft rejection and autoimmune and allergic diseases. We describe clear and reproducible sensitization to nickel in mice reared under nickel-free conditions. Hypersensitivity was induced by injecting nickel sulfate intradermally into the flank skin and elicited by injecting the metal salt into the pinnae of the ears. The effectiveness of orally induced hyporesponsiveness could be inferred from a low degree of hypersensitivity obtained with mice raised and maintained in cages with nickel-releasing covers and water nipples. This mouse model for the assay of nickel hypersensitivity was used for oral tolerance studies by administrating non-toxic doses of nickel sulfate in drinking water or intragastrically prior to sensitization. In these animals, the development of delayed-type hypersensitivity was suppressed in a dose-dependent way, and the hyporesponsiveness could be transferred by CD8+ cells. The antigen specificity of this oral tolerance could be demonstrated by the concomitant use of sensitization and challenge procedures for nickel and chromium. The hypersensitivity assay described provides a versatile, highly reproducible experimental model to study immunoregulation of oral tolerance to clinically relevant metal allergens.

Administration, Oral↗

PubMed1999

Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: A double-blind, placebo-controlled trial.

BACKGROUND: The local (noninjection) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy, and their mechanisms of action are currently undergoing investigation. OBJECTIVE: We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species. METHODS: Thirty patients with Parietaria species-induced rhinoconjunctivitis (13 with mild intermittent asthma) were randomly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course. We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment. RESULTS: The investigated immunotherapy was well tolerated, and no side effects were recorded. A significant reduction of the symptom score (P =.016) and drug intake score (P =. 008) after immunotherapy was observed only in the active group. A decrease of the cumulative score was observed also in the placebo group (P =.046), but the significance was clearly higher (P =.006) in the active group. In the active group a reduction of neutrophils (P =.001), eosinophils (P =.01), and intercellular adhesion molecule 1 expression (P =.04) after specific nasal challenge was also detected. CONCLUSION: The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinically effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen.

Administration, Sublingual↗

PubMed1997

Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen.

BACKGROUND AND OBJECTIVE: The mechanisms operative in specific immunotherapy (SIT) of Type I allergy are not completely understood. In the present study we evaluated immunological changes during SIT in pollinosis. METHOD: Eight patients suffering from pollinosis (monosensitized to grass pollen) were treated with conventional SIT. All subjects had IgE specific for Phl p 1, a major allergen of timothy grass. In vitro changes in the immunological reactivity to grass pollen extract and to recombinant Phl p 1 were evaluated. Subjects were examined at three occasions: before, after 3 months and after 1 year of SIT. RESULTS: Serological analysis revealed a marked increase of grass pollen- and Phl p 1-specific IgG, titres of specific IgE did not change significantly. Lymphoproliferative responses to grass pollen extract and rPhl p 1 were reduced already after 3 months of treatment. Accordingly, the cloning efficiency for Phl p 1-specific T-cell clones (TCC) dropped markedly in all patients. The majority of allergen-specific TCC raised before SIT revealed a TH2-like pattern of cytokine production, TCC established after SIT revealed TH1 characteristics. This shift was due to a decrease in IL-4 rather than an increase in IFN-production by T cells. Investigations of the epitopes recognized by T cells before and after SIT did not reveal the outgrowth of new ('protecting') specificities. We could not observe induction of allergen-specific CD8+ lymphocytes (supressor cells). CONCLUSION: Our data indicate that -- on the level of TH lymphocytes -- SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation.

Adult↗

PubMed2006

Therapeutic effects of DNA vaccine on allergen-induced allergic airway inflammation in mouse model.

Vaccination with DNA encoding Dermatophagoides pteronyssinus group 2 (Der p 2) allergen previously showed its effects of immunologic protection on Der p 2 allergen-induced allergic airway inflammation in mice. In present study, we investigated whether DNA vaccine encoding Der p 2 could exert therapeutic role on allergen-induced allergic airway inflammation in mouse model and explored the mechanism of DNA vaccination in asthma specific-allergen immunotherapy. After sensitized and challenged by Der p 2, the BALB/c mice were immunized with DNA vaccine. The degrees of cellular infiltration were scored. IgE levels in serum and IL-4/IL-13 levels in BALF were determined by ELISA. The lung tissues were assessed by histological examinations. Expressions of STAT6 and NF-kappaB in lung were determined by immunohistochemistry staining. Vaccination of mice with DNA vaccine inhibited the development of airway inflammation and the production of mucin induced by allergen, and reduced the level of Der p 2-specific IgE level. Significant reductions of eosinophil infiltration and levels of IL-4 and IL-13 in BALF were observed after vaccination. Further more, DNA vaccination inhibited STAT6 and NF-kappaB expression in lung tissue in Der p 2-immunized mice. These results indicated that DNA vaccine encoding Der p 2 allergen could be used for therapy of allergen-induced allergic airway inflammation in our mouse model.

Animals↗

PubMed1997

Recombinant allergen fragments as candidate preparations for allergen immunotherapy.

BACKGROUND: Lately, renewed interest has arisen in the new forms of allergen immunotherapy because they may offer alternatives for drug treatment. OBJECTIVE: The purpose of this study was to develop a well-characterized preparation of the main respiratory cow dander allergen, Bos d 2, with attenuated allergenic activity. METHODS: The immunologic characteristics of Bos d 2 preparations were studied by indirect IgE ELISA, ELISA inhibition, Western blotting, histamine release, skin prick tests, and the proliferation tests of allergen-specific T-cell clones. RESULTS: The complete recombinant Bos d 2 was observed to bind effectively, IgE of cow-allergic patients in indirect ELISA. In other experiments, the IgE-binding capacity of recombinant Bos d 2 proved to be lower compared with native Bos d 2. When the two overlapping recombinant fragments of Bos d 2 (corresponding amino acids 1-131 and 81-172, respectively) covering the whole molecule were compared with the complete recombinant Bos d 2 with several methods, only a low level of residual reactivity was observed. For example, recombinant fragments could not bind antibody at all in ELISA inhibition tests retaining, however, some reactivity in skin prick tests. In contrast, the fragments were able to stimulate vigorously Bos d 2-specific T-cell clones. CONCLUSION: The approach we have taken may offer a simple and reproducible way to produce hypoallergenic preparations for immunotherapy, circumventing simultaneously some of the problems of other experimental methods such as individual T-cell epitope recognition in peptide-based immunotherapy.

Adult↗

PubMed2000

Changes in cytokine production in vitro during the early phase of birch-pollen immunotherapy.

The kinetics of the immunological mechanisms during allergen-specific immunotherapy (IT) has not been thoroughly evaluated. In this investigation we study the changes in T-cell responses during the early phase of IT. Ten patients (IT group) with birch-pollen allergy were treated with conventional IT. Blood samples were collected at regular intervals for specific immunoglobulin (Ig)E measurements and preparation of peripheral blood mononuclear cells (PBMC). Seven allergic control patients (AC group) were included during the subsequent birch-pollen season. The PBMC were stimulated with birch-pollen extract or tetanus toxoid (TT) and mitogens. After a short decrease, probably owing to seasonal variation, the birch-pollen-specific proliferation and the interleukin (IL)-4, IL-5, and IL-10 production significantly increased when reaching the maintenance dose and during the subsequent pollen season. The increase in IL-4 correlated with a temporary increased serum level of birch-pollen-specific IgE. Interestingly, also the TT-specific response was affected by IT, resulting in weaker, but in time similar, changes in proliferation and cytokine production as in the birch-pollen-specific response. We speculate that the early phase of IT might lead to systemic changes in the capacity of Th2-like cytokine production, and that the early increase in allergen-specific IgE is a consequence of enhanced IL-4 production.

Adult↗

PubMed1999

Modified T-cell activation pattern during specific immunotherapy (SIT) in cat-allergic patients.

OBJECTIVE: The aim of the study was to analyse early effects of specific immunotherapy (SIT) on immune functions in cat-allergic patients. METHODS: Immunological responses of peripheral blood mononuclear cells from eight cat-allergic patients were analysed before and after SIT in comparison with 11 nonallergic controls. Cells were stimulated in vitro with either bacterial superantigen, mitogen, or cat allergen. Production of IL-12 and TH1/TH2 cytokines was analysed by ELISA and lymphocyte subset distribution was assessed by flow-cytometry. RESULTS: We found a significantly reduced secretion of IL-12 (P < 0.05) from cells of allergic individuals compared with the controls. This finding was associated with significantly lower IFN-gamma production after stimulation with allergen (P < 0.05) that did not increase during SIT. However, no significant differences were seen after stimulation with mitogen indicating an allergen specific IFN-gamma secretion response in allergic individuals. Prior to SIT IL-5 production was significantly higher in cells of allergic donors stimulated with allergen < 0.005 or mitogen (< 0.05). After reaching the maintenance dose for SIT, allergen-induced IL-5 production returned to normal levels, whereas it remained elevated after stimulation with mitogen. These changes were associated with a reduced frequency of CD45 RO T cells following SIT. CONCLUSION: These results suggest that SIT exerts early effects on allergen-specific T-cell responses with selective inhibition of the up-regulated TH2 immune response.

Allergens↗

PubMed1994

Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.

Oral tolerance is a long recognized method to induce peripheral immune tolerance. The primary mechanisms by which orally administered antigen induces tolerance are via the generation of active suppression or clonal anergy. Low doses of orally administered antigen favor active suppression whereas higher doses favor clonal anergy. The regulatory cells that mediate active suppression act via the secretion of suppressive cytokines such as TGF beta and IL-4 after being triggered by the oral tolerogen. Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response. Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ. Thus it may not be necessary to identify the target autoantigen to suppress an organ-specific autoimmune disease via oral tolerance; it is necessary only to administer orally a protein capable of inducing regulatory cells that secrete suppressive cytokines. Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis (EAE), uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse. In addition, orally administered alloantigen suppresses alloreactivity and prolongs graft survival. Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity.

Administration, Oral↗

PubMedDate not supplied

Immunological basis of oral tolerance.

Oral tolerance may be defined as a specific reduction in the immune response brought about by feeding an antigen. It has been reviewed by us recently as a possible treatment of rheumatoid arthritis. It has a respectably long history as an experimental phenomenon, in the course of which a variety of modes of action have been proposed. More recently the following mode of action has been proposed: An antigen, for instance foreign type II collagen, passes from the lumen of the gut across multifold-cells (M-cells) lying under Peyer's patches, and thence into antigen-presenting cells within the patches. These cells then activate a local population of T cells which specializes in the secretion of transforming growth factor-beta (TGF beta) and IL-4. Following activation a few of these cells wander out through the lymphatics and blood stream, and thence through tissue, until they again find type II collagen, their recall antigen. What they find in a patient with inflammatory arthritis, it is believed, is self-type II collagen exposed within the inflamed joints, which they recognize via its cross-reaction with the foreign collagen which had originally activated them. The specialized T cells are then stimulated by their recall antigen to secrete TGF beta and IL-4. These inhibitory cytokines suppress the activity of neighboring disease-inducing Th1 cells ("bystander suppression"). The latter cells presumably recognize one or more autoantigens, the nature of which is unknown. It need not be type II collagen, which figures in the whole story only as an organ-specific antigen, which lures the suppressive T cells to the right place.

Administration, Oral↗

PubMed1986

Clinical and immunological effects of oral immunotherapy with a standardized birch pollen extract.

Oral immunotherapy (IT) was evaluated in a pilot study in two centres in children aged 8-15 years with allergic rhinoconjunctivitis. High doses (up to 20 X 10(6) BU monthly) of a defined freeze-dried birch pollen extract administered in enteric-coated gelatine capsules were given either daily for seven consecutive days every month or once weekly. Symptom scores, as assessed by sneezing, dripping and blockage of the nose, and redness, itching and swelling of the eyes, were significantly lower in treated patients compared to untreated, or placebo treated controls after 3 to 5 months of therapy. In all the 16 treated, but only in three of eight untreated patients, the scores were lower during the pollen season 1982 than during the pollen season preceding the treatment period, despite comparable pollen counts during the two seasons. One year after beginning treatment the reactivity in conjunctival provocation tests was decreased about 10-fold (P less than 0.001) in the patients receiving more than 2 X 10(5) BU monthly compared to about two-fold in patients receiving lower doses, or placebo. Increased levels of IgE antibodies directed against birch pollen were recorded in the serum and saliva of most patients after 3-4 months of active IT. In contrast, IgG antibody responses were poor in most of the patients. Side effects, particularly from the gastrointestinal tract, appeared in all treated children. In one of them a systemic reaction occurred during IT. The study indicates that properly performed oral IT with a potent birch allergen extract in enteric-coated capsules may be effective.

Administration, Oral↗

PubMed1987

Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology.

Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 micrograms usually protects from life-threatening reactions. However, in some patients 200 micrograms are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.

Adult↗

PubMed1983

Effects of immunological sensitization on the responses and sensitivity of guinea pig airways to bronchoconstrictors. Modulation by selective inhibition of arachidonic acid metabolism.

The force generated by tracheal spirals and lung parenchymal strips from normal and ovalbumin-sensitized guinea pigs was measured in vitro, after challenge with histamine, carbachol, leukotriene (LT) C4, LTD4, or a prostaglandin endoperoxide analog (U-44069). The responses and sensitivity of airway tissues to the above agonists were identical in normal and sensitized animals. Treatment of tracheal spirals with indomethacin (8.5 microM), phenidone (185 microM), and nordihydroguaiaretic acid (NDGA: 30 microM) reduced resting tension (tone) equally in both normal and sensitized trachea, but did not affect lung parenchymal strips from either group. The responses of tracheal spirals from normal and sensitized animals to low concentrations of histamine, carbachol, LTC4, and LTD4 were reduced or abolished by treatment with the above inhibitors. Responses to higher concentrations of the same agonists were significantly enhanced. In contrast, treatment of normal and sensitized trachea with indomethacin (2.8 and 8.5 microM) did not abolish or reduce the effects of low concentrations of U-44069. However, an enhancement of the effect of high concentrations occurred only on normal tracheal spirals, even though the control tissues from each group responded identically with U-44069 in the absence of any inhibitor. Parenchymal strips increased in sensitivity to histamine, but not carbachol, as a result of time, vehicle, or prior exposure to the drug. Inhibitor treatment did not affect sensitivity or responsiveness of parenchyma to histamine, carbachol, and U-44069, but the contractile activity of LTD4 on both normal and sensitized lung parenchymal strips was reduced by indomethacin, NDGA, and phenidone. We conclude that ovalbumin sensitization does not induce hyperreactivity of guinea pig airways.

Animals↗

PubMed1999

Immunohistochemical investigation of the cellular infiltrates at the sites of allergoid-induced late-phase cutaneous reactions associated with pollen allergen-specific immunotherapy.

BACKGROUND: Reduction in the size of the allergen-induced late-phase reaction (LPR) is seen as a consequence of successful allergen specific immunotherapy. OBJECTIVE: It was the aim of this study to characterize the cellular infiltrate at the sites of cutaneous LPR that may occur following injection of a depot pollen allergoid (Allergovit(R)) during immunotherapy and thereby determine the immunological nature of the response. METHODS: Punch biopsies were taken 24 h after subcutaneous injection of a depot pollen allergoid from eight patients that showed LPR and a further five patients that did not. Additional biopsies taken 24 h after injection of allergoid-free depot in the same patients served as controls. Immunoenzymatic labelling of the cryostat sections with different antibodies was performed with the APAAP technique. Results were expressed as cells/field (400 x magnification). RESULTS: Similar dermal cellular infiltrations were seen following depot allergoid injections in patients both with and without LPR. Patients with LPR showed statistically significant increases in total cells, CD4+ cells, CD11c+ cells, CD45RO+ cells, CD45RB+ cells and activated eosinophils at the reactions sites as compared with control sites. In patients without LPR CD11c+ cells, HLA-DR+ cells and CD45RA+ T cells increased significantly. CD8+, CD1a+, NP57+, CD23+ and CD25+ cells did not differ significantly in either group. CONCLUSION: These results indicate that activation of T cells, monocytes/macrophages and eosinophils at the sites of LPR following injection of depot allergoid are comparable with those following injection of allergen. Even in the absence of a cutaneous LPR, subsets of T cells and monocytes/macrophages increased. These cell activations may reflect events associated with the mechanisms of allergoid-based specific immunotherapy, and suggest that at least part of the late-phase reaction may be independent of IgE.

Adult↗

PubMed1997

Allergen induced cytokine profiles in type I allergic individuals before and after immunotherapy.

Allergen immunotherapy (IT) involves subcutaneous injections of increasing doses of specific allergen over a period of time. It is recognised as highly effective in the treatment of patients with allergic rhinitis. However, the specific immunological mechanisms by which IT achieves its effect have not been fully elucidated. Recent studies, have shown that the clinical effects following IT of allergic individuals is concomitant with a reduced production of IL-4 by allergen specific CD4+ T-cells. The aim of the present study was to gain better knowledge about the immunological mechanisms by which IT exerts its beneficial effects. For this purpose, peripheral blood mononuclear cells (PBMC) from ten individuals receiving birch allergen or placebo in an IT-study performed in a double-blind manner, were analysed for IL-4, IFN-gamma, IL-5 and IL-10 mRNA expression at the onset of the study and during the pollen season, during treatment. Both spontaneous and in vitro allergen-induced cytokine mRNA expression was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). Spontaneous expression of IL-4 mRNA could be detected in most of the allergic patients, but not in healthy donors. The IT-treated patients showed a decrease in the spontaneous expression of IL-4 mRNA during the pollen season as compared to at the onset of the study, while in patients receiving placebo the IL-4 mRNA expression increased or remained unchanged. Similar results were obtained after in vitro stimulation with allergen. This was in contrast to the results for IFN-gamma, which was readily detected in both patient groups with no significant differences between the groups at either timepoint. IL-5 was shown to be increased during the pollen season in both groups and thereby presumably not affected by allergen IT. Taken together, these observations suggest that the cytokine profiles in circulating T lymphocytes change as a consequence of allergen IT.

Allergens↗

PubMed2001

Allergic rhinitis and asthma: more similarities than differences.

Clinical epidemiological and pathophysiological studies suggest a strong functional and immunological relationship between the nose and the bronchi. Nasal stimulation, can induce bronchoconstriction by a proposed rhinobronchial reflex and inflammatory mediators originating from the nose could be inhaled and trigger bronchial inflammation. Bronchial provocation in sensitised subjects results in nasal inflammation through systemic circulation. There is an increased prevalence of asthma in patients with rhinitis relatively to patients without nasal complaints and allergic rhinitis patients have an increased risk to develop asthma. Nasal and bronchial co-morbidity is high, 75% of asthmatics have rhinitis and 20% to 40% of rhinitic patient suffer from asthma. In the World Health Initiative on Allergic Rhinitis and its effect on Asthma (ARIA) it is quoted that asthma and rhinitis are common co-morbidities suggesting the concept of one airway one disease. The term allergy rhinobronchitis has been proposed to link the association between asthma and rhinitis. The treatment of rhinitis and sinusitis is important for management of asthma. Treatment of chronic rhinitis not only reduces nasal inflammation obstruction and discharge but also can reduce lower airway hyperesponsiveness and symptoms of asthma. Treating nasal inflammation is a key point in asthma control. These data strength the functional and allergologial link between nose and bronchi. Nasal inflammation induced by nasal challenge in patients with rhinitis has the ability to also induce bronchial changes in some asthmatic patients.

Anti-Allergic Agents↗

PubMed2001

Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study.

BACKGROUND: Calcium phosphate-adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants. OBJECTIVES: A double-blind, placebo-controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five-grass-pollen extract adsorbed onto calcium phosphate for specific immunotherapy (IT). METHODS: Twenty-nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1-year study. During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG4 antibodies) were assessed before, during and after IT. RESULTS: The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during grass-pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P < 0.01, Mann-Whitney U-test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 vs. 102.3, P < 0.05, U-test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in grass pollen cutaneous reactivity in the actively treated group (P < 0.001). A significant increase in serum-specific IgG4 antibody response was observed in the IT group (3.1% before IT vs. 10.1% after IT, P < 0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group. CONCLUSION: Specific immunotherapy with calcium phosphate-adsorbed standardized grass pollen extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.

Adolescent↗